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Interaction between Neuronal Depolarization and MK-801 in SH-SY5Y Cells and the Rat Cortex
Yeni Kim1, Miran Seo, Yun-Il Lee
1Department of Biochemistry and Molecular Biology, Seoul National University College of Medicine, Seoul, Korea.
Objective:
The interaction between MK-801, a model of psychosis and KCl-induced depolarization or electroconvulsive shock (ECS), a therapeutic model of electroconvulsive therapy (ECT), was investigated in SH-SY5Y cells and the rat frontal cortex.
Methods:
SH-SY5Y cells were pretreated with 1 microM MK-801 for 15 min, followed by cotreatment with 100 mM KCl for 5 min. MK-801 was reintroduced after the KCl was washed out, and the samples were incubated before harvesting. For the experiments in rats, male Sprague-Dawley rats were treated with MK-801 followed by ECS. Immunoblot analyses of glycogen synthase kinase 3beta (GSK3beta) (Ser9), AKT (Ser473) and extracellular legulated kinase (ERK)1/2 in SH-SY5Y cells and the rat frontal cortex were performed.
Results:
KCl-induced neuronal depolarization resulted in the transient dephosphorylation of AKT (Ser473) and GSK3beta (Ser9), followed by increased phosphorylation of the enzymes in SH-SY5Y cells. Cotreatment with MK-801 and KCl inhibited the initial dephosphorylation of AKT and GSK3beta produced by KCl-induced neuronal depolarization. Similarly, ECS resulted in the transient dephosphorylation of AKT (Ser473) and GSK3beta (Ser9), whereas cotreatment with MK-801 inhibited the initial dephosphorylation of AKT (Ser473) and GSK3beta (Ser9) produced by ECS in the rat frontal cortex. No significant interaction was observed between MK-801 and KCl in the dephosphorylation of ERK1/2.
Conclusion:
These results suggest that an antagonistic interplay between MK-801 and neuronal depolarization by KCl or ECS is involved the regulation of AKT (Ser473) and GSK3beta (Ser9) phosphorylation.
Insights
MK-801, a psychosis model, antagonizes neuronal depolarization effects on AKT and GSK3beta phosphorylation in cells and rat brains. This interaction impacts key signaling pathways relevant to neurological conditions.
Area of Science:
- Neuroscience
- Pharmacology
- Molecular Biology
Background:
- Psychosis models like MK-801 and neuronal depolarization stimuli (KCl, ECS) are crucial for understanding brain function.
- AKT and GSK3beta signaling pathways play significant roles in cellular regulation and are implicated in various neurological disorders.
Purpose of the Study:
- To investigate the interaction between MK-801 and neuronal depolarization induced by KCl or electroconvulsive shock (ECS).
- To examine the effects on the phosphorylation of AKT (Ser473) and glycogen synthase kinase 3beta (GSK3beta) (Ser9) in SH-SY5Y cells and rat frontal cortex.
Main Methods:
- SH-SY5Y cells and rat frontal cortex were used to model psychosis and neuronal depolarization.
- Immunoblot analysis was performed to assess the phosphorylation levels of AKT, GSK3beta, and ERK1/2.
Main Results:
- KCl-induced depolarization and ECS caused transient dephosphorylation of AKT (Ser473) and GSK3beta (Ser9).
- MK-801 cotreatment inhibited this initial dephosphorylation in both cellular and animal models.
- No significant interaction was observed with ERK1/2 phosphorylation.
Conclusions:
- MK-801 exhibits an antagonistic interplay with neuronal depolarization (KCl or ECS).
- This interaction specifically influences the regulation of AKT (Ser473) and GSK3beta (Ser9) phosphorylation.
- Findings provide insights into the molecular mechanisms underlying psychosis and potential therapeutic targets.
